The connection between iv drug abuse and AIDS and AIDS-related diseases has made detailed studies of the relationships between the opioid system and the immune system essential, especially in terms of the actions of opioids on immune competence. Over the past few years, reports indicating that opioids can produce alterations in the immune system have increased to the point that there is no longer any question about this action. However, the extent to which this occurs requires further evaluation. Our knowledge about the cell types targeted and the types of opioid receptors involved is growing. Our original hypothesis was that opioids alter selective components of the immune system, resulting in the compromising of immune competence, and that the various types and subtypes of opioid receptors play a differential role in these effects. Our work strongly supports this hypothesis and indicates that all of the classical types of opioid receptors can be suppressive. Based on our research, we have proposed new hypotheses. Using different dosing regimens, we will determine the effects of opioids on resistance to infection, the opioid receptor type involved, the opioid-mediated alterations in cytokine production, the relationship between opioid receptor expression and immune cell function and, by using molecular techniques, the mechanisms involved in opioid effects on immune cells. A range of methods and techniques will be used, spanning whole animal to molecular approaches. Studies conducted in animals will assess, among other measures, the consequences of opioid- induced alterations in the cellular and humoral arms of the immune system of the bacteria-infected host; while the basic mechanisms involving receptors and cells will be investigated with molecular techniques. These studies are of significance in that they can provide a scientific basis for understanding how opioids adversely affect immune competence and susceptibility to infectious diseases. It will allow us to better relate laboratory findings in the mouse model to patterns of drug abuse in addicts. The focus on elucidation of receptor subtypes and interactions of opioids which act at different receptor subtypes will not only tell us more about the possible role of the endogenous opioid system in immunoregulation, but will provide necessary background information as new medications that act on the different types and subtypes of opioid receptors are developed and introduced into clinical medicine.